Beyond TNM: Tumor Volume as a Prognostic Marker in Laryngeal Cancer.

Uralov, Daniel; Iovine, Chiara; Di Cristina, Luciana; Paderno, Alberto; Giannitto, Caterina; Canali, Luca; Gullà, Federica; Tosi, Elena et al. · Laryngoscope · 2026

prospective_cohort · Level II

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Abstract

The objective of this study is to determine whether radiologic tumor volume adds prognostic value for overall survival (OS) and disease-free survival (DFS) in laryngeal squamous cell carcinoma (LSCC) and to evaluate associations with T stage, nodal status, histologic grade, subsite, and treatment modality. Patients with cT2-T4 LSCC treated with curative intent between 2018 and 2024 were included. Tumor volumes derived from CT, MRI, or radiotherapy planning contours were analyzed as continuous and binary variables using a threshold identified by log-rank maximization. Survival was assessed with Kaplan-Meier methods and Cox proportional hazards models. Eighty-eight patients were included (39.8% surgical and 60.2% nonsurgical). Median tumor volume was 3.7 cm<sup>3</sup> (range 0.03-51.3 cm<sup>3</sup>). Volume threshold of 22.498 cm<sup>3</sup> was associated with a 3.6-fold increase in mortality (60.0% vs. 16.7%; p < 0.001), with significantly worse OS and DFS in the high-volume group (both p < 0.001). On multivariable analysis, high tumor volume remained independently associated with OS after adjustment for age, T stage, and nodal status (HR = 9.66, 95% CI: 2.56-36.39). Tumor volume correlated with T stage (Spearman ρ = 0.569, p < 0.001), and node-positive tumors were larger than node-negative tumors (median 5.6 cm<sup>3</sup> vs. 2.6 cm<sup>3</sup>; p = 0.017). Supraglottic and transglottic tumors had larger volumes than glottic and higher-grade tumors were associated with larger volumes. Nonsurgical patients had smaller tumors than surgical patients. Tumor volume was independently associated with survival outcomes in LSCC and may improve risk stratification beyond TNM classification alone. A threshold of 22.498 cm<sup>3</sup> identifies a high-risk subgroup and warrants prospective validation for integration into staging and treatment planning.